Abstract

BackgroundCancer cells, including colorectal cancer ones (CRC), release high amounts of nanovesicles (exosomes), delivering biochemical messages for paracrine or systemic crosstalk. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression.ResultsCRC exosomes induce in cMSCs: i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of CEA. Colon cancer derived MSCs, which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes.Materials and MethodsTissue specific colonic (c)MSCs were exposed to primary or metastatic CRC exosomes and analysed by light and electron microscopy, proliferation in 2D and 3D cultures, migration and invasion assays, Western blot and confocal microscopy for vacuolar H+-ATPase expression.ConclusionsCRC exosomes are able to induce morphological and functional changes in colonic MSCs, which may favour tumor growth and its malignant progression. Our results suggest that exosomes are actively involved in cancer progression and that inhibiting tumor exosome release may represent a way to interfere with cancer.

Highlights

  • Colon cancer remains a leading cause of death in the western world [1]

  • colorectal cancer ones (CRC) exosomes induce in colonic mesenchymal stromal cells (cMSCs): i) atypical morphology, higher proliferation, migration and invasion; ii) formation of spheroids; iii) an acidic extracellular environment associated with iv) a plasma membrane redistribution of vacuolar H+-ATPase and increased expression of carcinoembryonic antigen (CEA)

  • Colon cancer derived Mesenchymal stromal cells (MSCs), which were isolated from tumor masses, produce umbilicated spheroids, a future frequently observed in the inner core of rapidly growing tumors and recapitulate the changes observed in normal colonic MSCs exposed to CRC exosomes

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Summary

Introduction

Colonic epithelial cells are the second fastest proliferating cells in the human body, are exposed to contaminants in food, and intensely interact with colonic microbiota. Organ development and injured tissue repair, stem cells are able to oscillate, in a highly coordinated fashion, between epithelial and mesenchymal states [4]. In the adult this function can be retrieved by epithelial cancer cells where epithelial-mesenchimal transition constitutes a recognized mechanism for the loss of tight junctions, the detachment of malignant cells from the primary mass, their movement through newly generated extracellular matrix toward the blood vessel walls, the crossing of the vessel wall and the colonization of distal tissues/organs [4]. Mesenchymal stromal cells (MSCs) have been shown to play contradicting roles in tumor progression

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